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Industrialized semi-synthesis process of vincamine

A technology of vincamine and nitrogen oxides, applied in the direction of organic chemistry, can solve the problems of high production equipment requirements, high cost, and low chemical atom economy, and achieve simple equipment, large economic and social benefits, and environmentally friendly production procedures Effect

Inactive Publication Date: 2013-08-07
彭学东
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In summary, there are some following problems in the method of producing vincamine at home and abroad at present: chemical atom economy is low, and total yield is less than 10%, and produced chemical waste will certainly cause very big burden to environment; high, will inevitably lead to higher costs, and the production enterprise will bear high operational risks; all synthetic routes are more than 10 steps, and all have high requirements for production equipment, which will increase the fixed cost of production enterprises

Method used

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  • Industrialized semi-synthesis process of vincamine

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Embodiment 1

[0022] The synthesis of embodiment 1 Changchun Fermin

[0023] Weigh 5.0 kg of tabonin hydrochloride into a 100 L stainless steel reaction kettle, add 50 L of 75% ethanol, and stir to dissolve at room temperature. Then add 250g of Raney nickel, immediately feed hydrogen, stir after 0.5h, and control the hydrogen pressure to 1.1atm, and react for 8h. After the reaction was completed, nitrogen gas was passed through for 10 minutes, the catalyst was removed by filtration, and the crude product of vinbromin was obtained by concentration. Crystallization with ethyl acetate-ethanol gave 4.8 kg of vinbromin hydrochloride with a purity greater than 99.0%, with a yield of 96%.

Embodiment 216

[0024] Synthesis of embodiment 216-hydroxyl-vinporin oxide

[0025] Take 5.0 kg of vinchun phermin hydrochloride and place it in a 100 L stainless steel reaction kettle, add 50 L of 1,3-dioxane, stir and dissolve at room temperature. Filled with nitrogen protection, protected from light and reacted at room temperature for about 16 hours. The progress of the reaction was detected by TLC, until the Changchun Fermin intermediate basically disappeared, and the nitric oxide intermediate was generated. Add 5% NaHCO to the reaction solution 3 The solution was free of bubbles, and the excess peroxyacid and the generated acid were removed. Separate the organic phase, extract twice with 20 L of dichloroethane, combine the organic phases, dry with 500 g of anhydrous sodium sulfate overnight, and concentrate under reduced pressure to obtain crude 16-hydroxy-vinpophormin nitrogen oxide as an oily substance. Then crystallized with dichloromethane-acetone to obtain 4.0 kg of nitrogen oxid...

Embodiment 3

[0026] The synthesis of embodiment 3 vincamine

[0027] Put 5.0kg of 16-hydroxy-vinfofermin nitrogen oxide in a 100L stainless steel reaction kettle, add 60L of trichloroacetic acid, stir and dissolve at a temperature of about 0°C, then add 3.0kg of triphenylphosphine, and reflux for about 3 hours. The progress of the reaction was detected by TLC until the nitric oxide intermediate disappeared substantially. Cool the reaction solution, add an equal amount of ice water, and wash away triphenylphosphine oxide with dichloroethane. The aqueous phase was then adjusted to pH 8-9 with 1% NaOH, extracted twice with dichloromethane, the combined organic phases were concentrated to 20 L volume, and decolorized by adding activated carbon for 30 min. The organic phase was obtained by filtration, dried overnight with 500 g of anhydrous sodium sulfate, and a certain amount of methanol was added to the mother liquor to crystallize to obtain crude vincamine. The crude product was recrystall...

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Abstract

The invention relates to a semi-synthesis process for producing vincamine by taking tabersonine as a raw material. The high-purity vincamine with the content of over 99.0 percent is obtained by performing catalytic hydrogenation, peroxidation, rearrangement, crystallization and recrystallization on the tabersonine. Based on the tabersonine, the total yield of the vincamine is 55.3 percent. The semi-synthesis process has the characteristics of low cost, high yield, short time and simple and safe operation, and is completely suitable for industrialized mass production.

Description

technical field [0001] The invention relates to the synthesis of vincamine (vincamine), a drug for treating cardiovascular and cerebrovascular diseases, in particular to the purification of the semi-synthetic raw material vincamine, the synthesis of the intermediate vincadifamine, and the synthesis of the intermediate vincadifamine nitrogen oxide Synthesis and industrial scale purification process of vincamine. Background technique [0002] Vincamine is a monoindole alkaloid with strong physiological activity. Early foreign studies focused on its hypotensive activity. Because it can penetrate the blood-brain barrier, it was later found that it has a good effect on dilating blood vessels and increasing cerebral blood flow, but has no effect on the heart, blood vessels, and blood pressure. It is currently the first-line drug for the treatment of cerebral ischemia, and its clinical indications include cerebrovascular disorders, cerebral embolism, cerebral thrombosis, and hemor...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/20C07D461/00
Inventor 彭学东
Owner 彭学东
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